Other potassium channels play a role in phase 2 of the action potential. These potassium channels are characterized as delayed iK channels. They are closed during phase 4 and are activated very slowly by the potentials that prevail toward the end of phase 0. Hence, activation of these channels tends to increase gK very gradually during phase 2. These channels play only a minor role during phase 2, but they contribute to the process of final repolarization (phase 3), as described in the section “
Genesis of Repolarization (Phase 3) .” There exist two types of iK channels, classified according to their rates of activation: The more slowly activating channel is designated the iKs channel, and the more rapidly activating channel is designated the iKr channel (see
Fig. 16.8). The
Nav1.5 SCN5A
Cav1.2 CACNA1C
ICa,L
IK1 Ito,1 Ito,2 IKr IKs
Kir2.1/2.2 Kv4.2/4.3 Kv1.4/1.7 •Fig. 16.8 Changes in Ion Currents During the Various Phases of the Action Potential in a Fast-Response Cardiac Ventricular Cell. Upper panels, Depolarizingioncurrents.Lower panels, Repolarizingioncurrents.TheinwardcurrentsincludethefastNa+ (iNa)andL-typeCa++ (iCa,L)currents.OutwardcurrentsareiK1,ito,andtherapid(iKr)andslow(iKs)delayedrectifierK+ currents.Theclonesandgenesfortheprincipalioniccurrentsarealsoincluded.(RedrawnfromTomaselliG,MarbánE.Cardiovasc Res. 1999;42:270.) duration of the action potential in myocytes in various regions of the ventricular myocardium is determined in part by the relative distributions of these iKr and iKs channels.
The action potential plateau persists as long as the efflux of charge carried mainly by K+ is balanced by the influx of charge carried mainly by Ca++ . The effects of altering this balance are exemplified by the action of the calcium channel antagonist diltiazem in a papillary muscle preparation (see
Fig. 16.7 ). With increasing concentrations of diltiazem, the plateau voltage becomes progressively less positive and the plateau duration diminishes. Conversely, administration of certain potassium channel antagonists prolongs the plateau substantially.
Genesis of Final Repolarization (Phase 3)
The process of final repolarization (phase 3) starts at the end •Fig. 16.9 Inward Rectified K+ of phase 2, when efflux of K+ from the cardiac cell begins to tricular Myocyte When the Potential Was Changed From a Holding exceed influx of Ca++ . As noted, at least three outward K+
Potential of −80 mV to Various Test Potentials. Positivevaluesalong currents (ito, iK, and iK1) contribute to the final repolariza tion (phase 3) of the cardiac cell (see
Figs. 16.3 16.8 inwardcurrents.Thepointatwhichthecurrenttraceintersectsthe x-axisisthereversalpotential(open circle); itdenotestheNernstThe ito, iKr, and iKs currents help initiate repolarization. equilibriumpotential(EK),atwhichpointthechemicalandelectrostaticThese currents are therefore important determinants of forcesareequal.Vm,membranepotential.(RedrawnfromGilesWR, the duration of the plateau. For example, the duration of
ImaizumiY.J Physiol [Lond]. 1988;405:123.) the plateau is substantially less in atrial myocites than in ventricular myocytes (